Regulatory Anticipation
Safety Assessment
Barbara J. Patterson

Regulatory Anticipation

When I hear the word anticipation, I can’t help but think of the first line in the song with the same title that Carly Simon made famous in the 1970’s: “We can never know about the days to come.”

That is where we are with the long-anticipated modernization of the Food and Drug Administration (FDA) Good Laboratory Practice (GLP) regulations.

The FDA published this document as an Advanced Notice of Proposed Rule in the Federal Register on December 21, 2010, more than two years ago.

Like any government regulation, there is a defined rulemaking process for proposing, assessing economic impact, commenting, reviewing comments and enacting the changes into law. And yes, the GLP regulations are law.

The FDA received 77 public comments and 12 private, which of course take time to evaluate.  Unfortunately, we have not had any indication of when this process will be done and when the true modernization of the GLPs will be enacted.

In the meantime, we do know that the proposed revisions focus on the introduction and emphasis of core requirements of a “Quality System” in a GLP environment, particularly as it relates to data integrity. The FDA has expressed a need to also reinforce the responsibilities of Testing Facility Management for all activities at the facility and ensuring there are standard operating procedures for all essential functions.

The term “Multi-site Study” has long been in place with the OECD principles, but now the GLPs (as proposed) will acknowledge specific concepts (e.g., study phase and the responsibilities of the assigned scientist). The FDA GLPs already assign responsibility to the Study Sponsor for notifying a contract research organization of its responsibility to conduct the study or phase under GLP. However, the proposed amendment clarifies the responsibilities of the Sponsor to include a more defined role with protocol development and approval. Other changes proposed in the amendment focus on Quality Assurance Unit (QAU) inspectional practices, Test and Control Article Characterization (acceptance of GMP process), sample storage container retention and Animal Welfare documentation review practices.

The FDA is also considering updating the regulation to reflect the use of electronic and computerized systems and believes that any modifications to the regulation to reference electronic/computerized systems should be general to accommodate changes and advances in technology.

Outside of the proposed modernization of the GLP regulations, no single topic has received as much attention as the management and issuance of the pathology report and the timing of the peer review activity. The FDA has repeatedly stated that the signed final pathology report is the raw data for the histopathology portion of a study. But industry is still unclear on whether peer review is considered to be a Quality Control (QC) or consultative process. Peer review does allow for an open exchange of expertise and efforts to move towards an agreed upon scientific conclusion. However, the FDA expects the process to be transparent and that the level of documentation of this scientific exchange is evident to assure the data integrity and unbiased results.

Industry questions have been posed recently about whether the Study Director and/or Sponsor can review a pathology report before it is signed. The FDA has said that the draft-reporting process should be transparent, suggesting that an SOP be developed for the review process which defines the scope and timing of the review (who reviews what) and how it will be documented. As clearly stated in the GLPs, the Study Director has overall responsibility for the technical conduct of the study, as well as for the interpretation, analysis, documentation and reporting of results and represents the single point of study control. Perhaps the modernization efforts will expand on these expectations.

In the meantime, we will sit and wait for the next steps of the revision process and the modernization of the GLPs. Just call it Regulatory Anticipation!